A case report of olmesartan‐associated sprue‐like enteropathy: Diagnosis and healing confirmed by capsule endoscopy

Abstract Herein, we describe a case of olmesartan‐related sprue‐like enteropathy in which improvement in villous atrophy was confirmed by small‐bowel capsule endoscopy (CE). We successfully treated a 66‐year‐old man with a chief complaint of loose diarrhea. The patient had persistent watery diarrhea 10 times a day and experienced a weight loss of 9 kg in 3 months. An abdominal computed tomography scan showed fluid retention in the small intestine. Blood test results revealed no inflammatory reaction. Esophagogastroduodenoscopy detected villous atrophy in the stomach and duodenum. Moreover, small‐bowel CE showed villous atrophy in about two‐thirds of the small intestine. Based on other examinations, hyperthyroidism, intestinal tuberculosis, intestinal amyloidosis, and intestinal malignant lymphoma were ruled out. Therefore, the patient was suspected of having an olmesartan‐related sprue‐like disease. Early after discontinuation of medication, diarrhea symptoms improved, and a repeat CE indicated improvements in small intestinal villous atrophy. Since the patient had been administered olmesartan for a long time and CE showed villous atrophy throughout the small bowel, we suspected him of having the olmesartan‐associated sprue‐like disease. The findings of gastric mucosa atrophy on esophagogastroduodenoscopy may lead to an early diagnosis of this disease. Olmesartan‐related sprue‐like enteropathy should be considered as a differential diagnosis in patients with chronic severe watery diarrhea.


INTRODUCTION
Olmesartan-related sprue-like enteropathy is a malabsorption syndrome characterized by chronic diarrhea and weight loss that develops after olmesartan initiation. The symptom onset often occurs from several months to years after starting this medication. 1 The number of cases of olmesartan-related sprue-like enteropathy is increasingly reported in Japan. [2][3][4][5] Herein, we describe a case of the olmesartan-related sprue-like disease in which improvement in villous atrophy was confirmed by small bowel capsule endoscopy (CE). In this case, gastric mucosal atrophy could be visualized by esophagogastroduodenoscopy.

CASE REPORT
A 66-year-old man was referred to our hospital by an outpatient clinic with a 60-day history of watery diarrhea. His family medical history was unremarkable. His bowel habits comprised persistent watery diarrhea 10 times per day. The patient had a history of hypertension, hyperlipidemia, and 6-year treatment with nifedipine (20 mg/day), olmesartan (20 mg/day), and atorvastatin (5 mg/day) prescribed at another hospital.

DISCUSSION
According to the World Health Organization report, over one billion people worldwide experience hypertension. It is the leading cause of premature death. Olmesartan has been widely used worldwide, including in Japan, since its approval as an antihypertensive drug by the Food and Drug Administration in 2002. 6 Olmesartan-associated sprue-like enteropathy was proposed by Tapia et al. in 2012 who reported 22 patients with this adverse effect. Symptoms include nausea, vomiting, diarrhea, weight loss, and electrolyte abnormalities common to celiac disease. The mean duration was 3.1 years (range, 0.5-7 years) between drug initiation and the onset of diarrhea. These symptoms have been reported to improve promptly after discontinuation of olmesartan. 1 In our case, as well, symptoms improved promptly after drug discontinuation. In addition, CE 1.5 months after discontinuation of olmesartan showed rapid improvement in small intestinal mucosal atrophy.
The clinical features of olmesartan-related sprue-like enteropathy from previously reported cases in Japan are summarized in Table 1. Our patient is the fifth Japanese patient documented to have olmesartanrelated sprue-like enteropathy and the first patient documented to have healed atrophic mucosa confirmed by CE. Olmesartan-associated sprue-like enteropathy is a disease that extensively affects the intestinal tract. Unlike other endoscopic procedures, small intestinal CE is extremely useful and unique because it allows a detailed examination of the entire small intestinal mucosa, which is difficult to evaluate using routine diagnostic endoscopy. Moreover, the procedure is painless, easy to perform, and repeatable.
The hypothesized mechanisms include the following: First, the expression of transforming growth factor-β, an anti-inflammatory cytokine that plays an important role in maintaining intestinal mucosal immunity, is suppressed by angiotensin (Ang) receptor blockers, increasing the levels of Ang II and resulting in a relatively elevated level of proinflammatory cytokines. 1,7 Second, Ang II is inhibited from binding to Ang II Type 1 receptors, which are present almost everywhere in the gastrointestinal tract and are thought to bind to Ang II Type 2 receptors and promote apoptosis, resulting in small intestinal villous atrophy. 8 However, it has been reported that symptoms disappeared after switching from olmesartan to losartan, 9 suggesting that there is a specific mechanism for olmesartan. Therefore, further research is required.
Esophagogastroduodenoscopy revealed diffuse mucosal atrophy. Based on blood tests, antibodies of H. pylori or autoimmune gastritis such as anti-parietal cell antibodies and anti-intrinsic factor antibodies were negative. Therefore, the patient was considered to have olmesartan-induced gastric mucosal atrophy. This disease also causes pathologically active chronic gastritis. 10 One of the differential diagnoses of atrophic gastritis should be considered drug-induced by olmesartan.
Based on our case, olmesartan-associated sprue-like enteropathy is often difficult to diagnose and should be considered one of the differential diagnoses of chronic severe watery diarrhea.

AC K N OW L E D G M E N T S
We would like to thank Editage (www.editage.com) for English language editing.

C O N F L I C T O F I N T E R E S T S
None.

F U N D I N G I N F O R M AT I O N
None.

E T H I C S S TAT E M E N T
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from the participant for publication of this case report.